[Childhood cancer in part of France: Key issues and organization of care in Corsica island]. / État des lieux des maladies onco-hématologiques pédiatriques en Corse et organisation des soins.

INTRODUCTION: In France, the management of pediatric cancers is carried out in reference hospitals that can delegate care to local health centres (LHC), forming "care networks". There is no LHC in Corsica, forcing children and their families to leave the island for all care in the reference centre. The aim of this study was to describe the situation in Corsica and to consider this organisation. METHODS: This is a descriptive preliminary study based on databases from the National Childhood Cancer Registry, "RHeOP" network and a patient questionnaire. We included over a period of 10 years all children with onco-hematological disease who resided in Corsica. RESULTS: The incidence of pediatric cancers since 2005 ranged from 5 to 12 new cases per year. The hospital centre of Timone (Marseille) was the reference centre for 73% of patients, followed by Nice University Hospital for 14%. Almost all the parents interviewed (90%) were in favour of creating an LHC and all of them highlighted many difficulties that, according to them, could be improved by the presence of a LHC in Corsica (organisation of travel, delay and distance from home…). However, there currently appears to be a lack of training for medical and paramedical staff to provide quality second-line care. CONCLUSION: The rates of pediatric onco-hematological diseases in Corsica may warrant the creation of an LHC on the island. Additional cost studies on the feasibility of an LHC in Corsica are needed to optimise the care and quality of life of these children and their families.

[Cerebral vasculopathy in children with sickle cell disease: Key issues and the latest data]. / Vasculopathie cérébrale de l'enfant drépanocytaire : points clés et nouveautés.

Cerebral vasculopathy is a common and severe complication of sickle cell disease in children. The pathophysiology consists of progressive damage to the basal intracranial arteries and cerebral microcirculation, while chronic anemia worsens exposure to cerebral hypoxia. It results in stroke and subclinical or poorly symptomatic ischemic lesions. Many clinical, biological, and radiological risk factors have been identified. The prevention strategy through systematic transcranial Doppler screening of large-vessel vasculopathy has revolutionized the management of this disease and has greatly decreased the risk of developing stroke. MRI-MRA is a complementary diagnostic tool for anatomical analysis of parenchymal and vascular lesions, which is used for chronic disease monitoring or in the context of an acute neurological event. New exploration opportunities are offered by submandibular Doppler sonography and indirect evaluation methods of cerebral oxygenation and perfusion. If chronic blood transfusion therapy is used to prevent the occurrence and recurrence of cerebral complications of sickle cell disease, only allogeneic hematopoietic stem cell transplantation can safely and definitively stop the transfusion program. It should therefore be proposed early, before irreversible cerebral or vascular lesions occur. Hydroxycarbamide treatment has recently emerged as a potential substitute for chronic transfusions for the maintenance of transcranial Doppler velocities, but only after an initial treatment by transfusions and provided there is close follow-up. In the long run, cerebral vascular damage can cause progressive cognitive impairment and disability, even in children without radiologically identified lesions, indicating the importance of systematic and repeated neuropsychological testing.

[High-resolution ultrasonography for differential diagnosis between nodular basal carcinoma and sebaceous hyperplasia of the face: A pilot study]. / Échographie cutanée haute résolution dans le diagnostic différentiel entre carcinome basocellulaire nodulaire et hyperplasie sébacée du visage: une étude pilote.

BACKGROUND: Clinical differential diagnosis between incipient nodular basal carcinoma (NBC) and sebaceous hyperplasia (SH) of the face is difficult in some cases. A comparative histological analysis of these two entities led us to the hypothesis that 20MHz high-resolution ultrasonography (HRUS) may enable differentiation between NBC and SH. PATIENTS AND METHODS: Seventy-seven facial tumours requiring histological confirmation to distinguish between NBC and SH were scanned using HRUS before excision. No other imaging technique was used. The ultrasound scans were submitted to two blinded reviewers who were asked to classify the ultrasound pictures of the tumours as either hypoechoic or isoechoic/hyperechoic. Hypoechogenicity was defined as a diagnostic criterion for NBC. RESULTS: Reviewer response reproducibility for 2 images of the same tumour was 90%. Both reviewers agreed regarding the echogenicity classification of an image in 87.4% of cases. The sensitivity of the procedure was 90.9% for detection of NBC and 89.4% for detection of malignant lesions. Specificity was 69.6% for detection of basal cell carcinomas and 78.8% for detection of malignant lesions. DISCUSSION: HRUS is a non-invasive examination technique with excellent sensitivity for the detection of NBC in differential diagnosis with SH. Hypoechogenicity is not specific to NBC. The sensitivity of HRUS in our study suffered as a result of ultrasonography difficulties regarding unexpected differential diagnoses of NBC as well as tumour localisation in seborrhoeic areas.

Optimization of an immunohistochemical method to assess distribution of tight junction proteins in canine epidermis and adnexae.

Epidermal tight junctions (TJs) have been well characterized in human medicine. Abnormality of these structures is involved in skin diseases such as atopic dermatitis. There is little information about the expression and distribution of TJ proteins in the canine skin. The aim of this study was to develop an optimal immunohistochemical method for assessment of the expression of TJ proteins in the skin of healthy dogs. Formalin-fixed and paraffin wax-embedded skin biopsy samples from healthy human and canine patients were used. Canine skin samples were from the inguinal region and the nasal planum. Immunohistochemistry was used to study the expression of zonula occludens-1 (ZO-1), occludin and claudin-1, -4 and -7. Heat-induced antigen retrieval with EDTA (pH 9.0) yielded the best labelling of TJ proteins. ZO-1 and occludin were expressed in the cytoplasm and along the keratinocyte membrane, while claudin-1 and -4 were mainly membrane in distribution. ZO-1, occludin and claudin-1 were detected in all epidermal layers with the exception of the stratum corneum, while claudin-4 expression was restricted to the stratum granulosum. Expression of claudin-7 was difficult to evaluate. There was no difference in labelling pattern between inguinal and nasal planum skin.

Paratuberculosis (Johne's disease) in cattle and other susceptible species.

Paratuberculosis (Johne's disease) is a widespread and costly disease. This consensus statement will summarize recommendations regarding diagnosis, control, and treatment of Johne's disease in cattle and other species. Each section of recommendations is followed by a statement that subjectively characterizes the strength of the supporting evidence. The role played by Mycobacterium avium subsp. paratuberculosis (MAP) in the pathogenesis has been a matter of controversy for many years. This statement concludes with an assessment of the evidence in favor of MAP as a potential zoonotic pathogen.

[Does the regional health care organization impact the outcome of infants born with congenital diaphragmatic hernia?]. / Hernie diaphragmatique congénitale : le devenir des enfants est-il lié aux modalités de prise en charge ?

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is a serious pathology that requires optimal management in very specialized health centers. French medical care organization is regionally based. Hence, evaluating local practices may help deliver clear information to parents before delivery. The aim of this study was to analyze the neonatal characteristics and the postnatal outcome of infants affected with CDH, treated within two different French perinatal health care networks. PATIENTS AND METHODS: Retrospective cohort study of infants with CDH, cared for in the Lorraine perinatal health care network (Réseau Périnatal Lorrain [RPL]) or at Édouard-Herriot Hospital (HEH) in Lyon, between 1997 and 2007. RESULTS: One hundred and twenty-seven newborns were included, 44 in the RPL and 83 in Lyon. Prenatal diagnosis of CDH was similar in RPL and at HEH; 47.7% of infants with CDH died in RPL vs 36.1% in HEH (P=0.2). Surgery delayed for more than 24h was more frequent in RPL (68.6% vs 31.7%; P<0.001), with a postoperative mortality rate of 31.4% vs 15.9%; P=0.08. In RPL, specialized medical follow-up was rare (33.3% vs 100%; P<0.001), while psychomotor retardation was more frequent (33.3% vs 5.7%; P=0.002). CONCLUSION: This study brings to light the diversity of care and outcome for infants affected with CDH in two French perinatal health care networks. These results may help improve both centers' practices. In Lorraine for instance, the follow-up of these vulnerable children can be improved.

[Interstitial pneumonia after infliximab therapy for psoriasis]. / Pneumopathie interstitielle subaiguë après traitement d'un psoriasis par infliximab.

BACKGROUND: Tumour necrosis factor (TNF)-alpha inhibitors are increasingly used for treatment of severe psoriasis. Hypersensitivity pneumonia is a rare but frequently fatal side-effect of such therapy that is unknown to most dermatologists. PATIENTS AND METHODS: A 68-year-old woman was hospitalized for subacute dyspnoea, fever, dry cough and basal chest pain 3 months after beginning infliximab therapy for severe psoriasis. Blood tests revealed an inflammatory syndrome and hypoxaemia. Thoracic computed tomography showed bilateral basal interstitial infiltrates with pleural effusion. The results of bronchoalveolar lavage and of the other microbiology testing were negative. Probabilistic treatment with amoxicillin/clavulanic acid and spiramycin was ineffective. We suspected drug-induced alveolitis and began corticosteroid therapy which improved dyspnoea, gas exchange and X-ray images. DISCUSSION: Hypersensitivity pneumonia is a potential pulmonary complication of anti-TNF alpha therapy and is frequently fatal. We report the first case of interstitial pneumonia secondary to infliximab given for severe psoriasis without any other pneumotoxic agents. Clinical features include dry cough, dyspnoea, and fever of acute or subacute onset. A diagnosis of allergic alveolitis was retained after elimination of other possible causes of the patient's interstitial pneumonia. CONCLUSION: The indications for anti-TNF agents are increasing in dermatology, and it is thus vital to consider their very rare but serious complications such as hypersensitivity pneumonia.

Determinants of serum zinc concentrations in a population of French middle-age subjects (SU.VI.MAX cohort).

BACKGROUND/OBJECTIVES: Few studies have been conducted on determinants of serum zinc concentration, especially in France. The aim of this study was to investigate the relationships between serum zinc concentrations, and age, education, living area and life style in a large sample cohort of French adults. SUBJECTS/METHODS: Blood samples were collected after 12-h fasting in French adults (7448 women, 35-65 years old and 4926 men, 45-65 years old) participating to the SUpplementation in AntioXidant VItamins and Minerals cohort at enrolment. Serum zinc was determined by flame atomic absorption. RESULTS: Serum zinc concentration was lower in women (mean: 12.9 µmol/l, 95% confidence interval: 9.2-16.6 µmol/l) compared with men (mean: 13.4 µmol/l, 95% confidence interval: 9.7-17.1 µmol/l, P<0.0001). In total, 10% of the women showed serum zinc values <10.7 µmol/l and 10% of the men showed serum zinc values <11.3 µmol/l. Age was negatively associated with serum zinc only in men (P=0.001). In women, a positive association between smoking and serum zinc concentration (P=0.0003), and a negative relationship between highest education level and serum zinc concentration (P=0.01) were observed. With regard to geographical areas, the highest serum zinc concentrations were found in the Center, and the lowest in the Southwest of France for both men and women. The association between serum zinc concentrations and food categories or macronutrient intake disappeared after stratifying by gender. CONCLUSIONS: Age, gender and geographic area seem the main determinants of serum zinc concentrations in this study.

Cinnamon improves insulin sensitivity and alters the body composition in an animal model of the metabolic syndrome.

Polyphenols from cinnamon (CN) have been described recently as insulin sensitizers and antioxidants but their effects on the glucose/insulin system in vivo have not been totally investigated. The aim of this study was to determine the effects of CN on insulin resistance and body composition, using an animal model of the metabolic syndrome, the high fat/high fructose (HF/HF) fed rat. Four groups of 22 male Wistar rats were fed for 12 weeks with: (i) (HF/HF) diet to induce insulin resistance, (ii) HF/HF diet containing 20 g cinnamon/kg of diet (HF/HF + CN), (iii) Control diet (C) and (iv) Control diet containing 20 g cinnamon/kg of diet (C + CN). Data from hyperinsulinemic euglycemic clamps showed a significant decrease of the glucose infusion rates in rats fed the HF/HF diet. Addition of cinnamon to the HF/HF diet increased the glucose infusion rates to those of the control rats. The HF/HF diet induced a reduction in pancreas weight which was prevented in HF/HF+CN group (p<0.01). Mesenteric white fat accumulation was observed in HF/HF rats vs. control rats (p<0.01). This deleterious effect was alleviated when cinnamon was added to the diet. In summary, these results suggest that in animals fed a high fat/high fructose diet to induce insulin resistance, CN alters body composition in association with improved insulin sensitivity.

[Diffusion-weighted MR imaging of the female pelvis]. / IRM de diffusion et pelvis féminin.

Due to technical advances (parallel imaging and new phased-array coils), diffusion-weighted MR imaging can be used to image the female pelvis. Diffusion-weighted (b=1000) images are now acquired as a complement to conventional sequences (T2W, dynamic T1W images after intravenous injection of gadolinium). Diffusion weighted imaging improves the detection of small uterine tumors and the visualization of small implants of peritoneal carcinomatosis, which could play a significant role for tumor staging. It is helpful for characterization of complex ovarian tumors: the absence of hyperintensity on b=1000 diffusion-weighted images has an excellent positive predictive value for a benign etiology. It could also be helpful to characterize endometrial lesions, to differentiate between endometrial polyp and carcinoma when hysteroscopy is not possible, and to differentiate uterine fibroid from sarcoma. Finally, diffusion-weighted imaging could be helpful to assess the response of uterine tumors to therapy and could confirm a good outcome following uterine artery embolization of uterine fibroids.

[Value of diffusion-weighted imaging in the evaluation of adnexal tumors]. / Evaluation de la séquence de diffusion pour l'étude des tumeurs annexielles.

PURPOSE: To determine the value of diffusion-weighted imaging (DWI) in the evaluation of adnexal tumors, especially to distinguish between malignant and benign tumors. Materials and methods. Fifty-four patients with pelvic tumors (32 malignant and 22 benign) were referred for MRI of the pelvis. DWI was obtained in all patients. Histological correlation was available in all cases. The signal of solid and cystic tumor components was evaluated on T2W and b=1000 DWI, and ADC values were obtained. RESULTS: T2W hypointensity or absence of hyperintense signal on b=1000 DWI sequences was suggestive of a benign tumor. Hyperintensity on b=1000 DWI sequences was strongly correlated with malignant lesions. ADC values did not appear to discriminate between malignant and benign tumors. Also, the signal intensity of cystic tumor components on DWI sequences was not helpful to distinguish between malignant and benign tumor. CONCLUSION: The evaluation of solid tumor components on DWI appears to be helpful for adnexal tumor characterization.

Serum selenium determinants in French adults: the SU.VI.M.AX study.

The objective of the present work was to assess the relationship between serum Se concentrations and environmental determinants (i.e. lifestyle, social activity, geographic region, urban status, education, familial status, physical activity, BMI, tobacco, and food and alcohol consumption). Baseline results from 13 017 subjects (7876 women aged 35-60 and 5141 men aged 45-60) who participated in the SU.VI.M.AX (Supplémentation en Vitamines et Minéraux Antioxydants) study were analysed. Fewer than 2 % of the volunteers had a serum Se status under 0.75 micromol/l, which has been quoted as the cut-off of biological Se sub-deficiency. Women had significantly lower serum Se concentrations than men (1.09 (sd 0.19) micromol/l (n 7423) and 1.14 (sd 0.20) micromol/l (n 4915), P<0.0001, respectively). Significant differences in serum Se concentrations were observed between geographic areas. In both sexes, the serum Se concentration increased with alcohol, meat and fish consumption, and decreased with smoking. In premenopausal women, the serum Se concentration was higher in contraceptive-pill users than in non-users. In women only, age was associated with increased serum Se concentrations, and obesity (BMI> or =30 kg/m2) was associated with decreased serum Se levels. In men, we observed a decrease in serum Se concentrations with increased consumption of vegetables and fruits. In conclusion, though few of the volunteers participating in the SU.VI.M.AX study had Se status in the sub-deficiency range, 83 % of women and 75 % of men had serum concentrations below the value considered optimal for glutathione peroxidase activity. The largest Se associations in both sexes were found with regions, smoking, alcohol, meat and fish consumption. Further studies are needed to understand the difference in Se status between genders.

Factors influencing blood concentration of retinol, alpha-tocopherol, vitamin C, and beta-carotene in the French participants of the SU.VI.MAX trial.

OBJECTIVES: The data was collected during the inclusion step of the SUpplémentation en VItamines et Minéraux AntioXydants (SU.VI.MAX) study. This article deals with the study's first stage before any supplementation. The collected data shows factors influencing blood vitamin concentrations and may reflect the vitamin status of volunteers. MATERIAL AND METHODS: A total of 12,741 volunteers were enrolled in the SU.VI.MAX study 7,713 women 35-60 years of age and 5,028 men 50-60 years of age. The serum concentrations of retinol, alpha-tocopherol, and beta-carotene were measured by HPLC, and vitamin C concentration was measured by spectrofluorimetry using a Technicon continuous flow analysis apparatus. The volunteers recorded their 24 h diet by means of a specific terminal that was connected to the main central computer of the SU.VI.MAX study. Volunteers recorded the food they consumed daily and estimated its quantity by comparing pictures of dishes. RESULTS: Retinol concentration was significantly higher in older volunteers, and was higher in male than in female volunteers. Smoking had no effect on serum retinol, but the latter was higher in the autumn than in the winter. Serum retinol concentrations were higher in the Southwest region and lower in the Ile-de-France and East-Centre regions. Serum alpha-tocopherol was slightly higher in older volunteers and also higher in male volunteers. Serum alpha-tocopherol was significantly lower in smokers, and former smokers showed intermediate levels. Like retinol, serum alpha-tocopherol was higher in the autumn, and higher in the Southwest as compared to the East-Centre Serum beta-carotene was slightly higher in younger volunteers, and concentrations were higher in female than in male volunteers. Tobacco smoking decreased serum beta-carotene, which was higher in the autumn, and higher in the East, West, and North regions. Serum vitamin C was higher in female volunteers, and was not age related. Serum vitamin C was lower in smokers, was season-dependant, but contrary to fat-soluble vitamins, concentrations were higher in the winter and spring. Serum vitamin C was higher in the Southeast and East-Centre, but lower in the North region. CONCLUSION: These results suggest that serum retinol concentrations depend on gender, age, seasons, and location of residence. Similarly, serum alpha-tocopherol concentrations were slightly influenced by age, but more by tobacco smoking, seasons, dietary intake, and location of residence. Serum concentrations of beta-carotene depend on gender, age, smoking status, dietary intake, and location of residence. Serum vitamin C concentrations depend on gender, age, smoking status, seasons, dietary intake, and location of residence. Contrary to beta-carotene, retinol concentrations were higher in male than in female volunteers. Such a reversed relation suggests a higher beta-carotene-retinol conversion in male volunteers.

Age-related oxidative stress and antioxidant parameters in middle-aged and older European subjects: the ZENITH study.

OBJECTIVE: Oxidative stress has been reported to increase with ageing. However, the data in healthy humans remain controversial and studies in free-living elderly people are scarce. The objective of the present study was to compare age-related oxidative stress in late middle-aged and older free-living subjects. DESIGN: The effect of ageing on oxidative stress and antioxidant parameters was investigated in 188 middle-aged subjects from Clermont-Ferrand (France) and Coleraine (UK), and in 199 older subjects from Grenoble (France) and Roma (Italy). Plasma thiol (SH) groups, define definition (TBAR's) and total glutathione (GSH), define definition (FRAP), and superoxide dismutase (SOD) activity were measured at baseline of the ZENITH study. RESULTS: Plasma SH groups and FRAP and, surprisingly, TBAR's were significantly lower in free-living older subjects compared to younger subjects (P < 0.001, P < 0.001, P < 0.01, respectively), but there was no significant differences in GSH levels. CONCLUSION: European free-living healthy older do not appear to be exposed to an acute oxidative stress. However, the highly significant positive correlation between plasma SH group oxidation or decreased FRAP and ageing is predictive of an increased risk of oxidative stress in older subjects. Moreover, the comparison between middle-aged and older subjects regarding oxidative stress parameters suggests also a progressive and slow decline of antioxidant status in healthy free-living older elderly and underline the impact on life-style factors on successful ageing.

Screening and recruitment procedure of late-middle aged and older subjects: the ZENITH study.

OBJECTIVE: To report the rational, design, recruitment, baseline characteristics and preliminary overview of volunteers in the ZENITH study. DESIGN: A multicentre prospective intervention study employing a randomised double-blind design. SETTING: Clermont-Ferrand, Theix (France), Coleraine (Northern Ireland), Grenoble (France), Rome (Italy). PARTICIPANTS: Healthy men and women middle-aged (55-70 y) and older volunteers (70-87 y). INTERVENTIONS: At baseline (prior to zinc (Zn) supplementation), all volunteers underwent a full clinical examination, anthropometric measurements, health and lifestyle questionnaire, Mini Mental State Examination, Geriatric Depression Scale, and biochemistry profile. RESULTS: In total, 842 volunteers (378 men and 464 women) were invited to take part in the study. A total of 49% of these volunteers were excluded on the basis of inclusion/exclusion criteria. In total, 433 participants were admitted to the Zn supplementation for 6 months. During this period, about 10% of volunteers dropped out from the study. CONCLUSIONS: A total of 387 subjects (197 male and 190 female subjects) successfully completed the supplementation phase of the ZENITH study.

Serum concentrations of beta-carotene, vitamins C and E, zinc and selenium are influenced by sex, age, diet, smoking status, alcohol consumption and corpulence in a general French adult population.

OBJECTIVE: To assess relationships between energy, nutrient and food intakes, alcohol consumption, smoking status and body mass index (BMI), and serum concentrations of beta-carotene, alpha-tocopherol, vitamin C, selenium and zinc. METHODS: Data on health status, alcohol consumption, smoking habits, anthropometric data and biochemical measurements were obtained in 1821 women aged 35-60 y and 1307 men aged 45-60 y, participant to the SU.VI.MAX Study. Data on dietary intake were available on a subsample who reported six 24-h dietary records during the first 18 months of the study. RESULTS: Women had higher baseline serum beta-carotene and vitamin C concentrations and lower concentration for serum vitamin E, zinc and selenium than men. In women, younger age was associated with lowered mean concentration of serum beta-carotene, vitamin E and selenium. In men, only differences were observed for serum zinc, which was lower in older men. Current smokers of both sexes had significantly lower concentrations of serum beta-carotene, vitamin C and selenium, and, only in women, of vitamin E, than nonsmokers. Alcohol consumers had lower concentrations of serum beta-carotene and higher selenium concentrations. Serum beta-carotene and vitamin C concentrations were lower in obese subjects. There were positive associations of dietary beta-carotene, vitamin C and E with their serum concentrations. Age, nutrient and alcohol intakes, serum cholesterol, BMI and smoking status explained 15.2% of the variance of serum beta-carotene in men and 13.9% in women, and 10.8 and 10.0% for serum vitamin C, and 26.3 and 28.6% for serum vitamin E, respectively. CONCLUSION: Serum antioxidant nutrient concentrations are primarily influenced by sex, age, obesity, tobacco smoking, alcohol consumption and especially dietary intake of those antioxidant nutrients.

Effect of two years' supplementation with natural antioxidants on vitamin and trace element status biomarkers: preliminary data of the SU.VI.MAX study.

The "SUpplementation en VItamines et Minéraux AntioXidants" (SU.VI.MAX) study is a randomized double-blind, placebo controlled, primary-prevention trial designed to test the efficacy of a daily supplementation with antioxidant vitamins (vitamin C, 120 mg; vitamin E, 30 mg; and beta-carotene, 6 mg) and minerals (selenium, 100 microg; and zinc, 20 mg) at nutritional doses (one to three times the daily recommended dietary allowances), in reducing the frequency of cancers and cardiovascular diseases. The study involves 12,735 eligible subjects (women aged 35-60 years, men aged 45-60 years) included in 1994 in France. They will be followed up for 8 years. The targeted population is the general population. The aim of this specific analysis is to assess the effect of 2 years of supplementation on biochemical indicators of vitamin and trace element on a subsample of 1000 subjects. The mean (+/- standard deviation) concentrations of plasma beta-carotene, alpha-tocopherol, vitamin C, selenium and zinc among participants who were randomly assigned to receive a daily supplementation with beta-carotene, vitamin E, vitamin C, selenium and zinc for 2 years were significantly higher than those who were assigned to receive placebo. Specifically, the mean concentrations among men in the intervention group were 0.86 +/- 0.70 micromol/L for beta-carotene, 35.3 +/- 9.3 micromol/L for alpha-tocopherol, 11.5 +/- 4.7 microg/ mL for vitamin C, 1.65 +/- 0.33 micromol/L for selenium, and 16.2 +/- 3.9 micromol/L for zinc. The mean concentrations among women in the intervention were 1.25 +/- 0.90 micromol/L for beta-carotene, 34.9 +/- 8.4 micromol/L for alpha-tocopherol, 12.6 +/- 4.0 microg/mL for vitamin C, 1.68 +/- 0.37 micromol/L for selenium, and 15.3 +/- 3.9 micromol/L for zinc. The values observed for beta-carotene and vitamin E in the supplementation group after 2 years of intervention are those that have been associated with the lowest risk of cancer in observational studies. They are definitely lower than concentrations reported in intervention studies showing an apparent negative effect of high levels of beta-carotene supplementation on the lung cancer incidence rate in high-risk subjects (initial level multiplied by 12-18). Data from the follow-up will ascertain if any plausible reduction in the incidence rate of cancers may be associated with such amounts of antioxidant agents.

Complexation of two proteic insect inhibitors to the active site of chymotrypsin suggests decoupled roles for binding and selectivity.

The crystal structures of two homologous inhibitors (PMP-C and PMP-D2v) from the insect Locusta migratoria have been determined in complex with bovine alpha-chymotrypsin at 2.1- and 3.0-A resolution, respectively. PMP-C is a potent bovine alpha-chymotrypsin inhibitor whereas native PMP-D2 is a weak inhibitor of bovine trypsin. One unique mutation at the P1 position converts PMP-D2 into a potent bovine alpha-chymotrypsin inhibitor. The two peptides have a similar overall conformation, which consists of a triple-stranded antiparallel beta-sheet connected by three disulfide bridges, thus defining a novel family of serine protease inhibitors. They have in common the protease interaction site, which is composed of the classical protease binding loop (position P5 to P'4, corresponding to residues 26-34) and of an internal segment (residues 15-18), held together by two disulfide bridges. Structural divergences between the two inhibitors result in an additional interaction site between PMP-D2v (position P10 to P6, residues 21-25) and the residues 172-175 of alpha-chymotrypsin. This unusual interaction may be responsible for species selectivity. A careful comparison of data on bound and free inhibitors (from this study and previous NMR studies, respectively) suggests that complexation to the protease stabilizes the flexible binding loop (from P5 to P'4).

Potential antioxidant effects of zinc and chromium supplementation in people with type 2 diabetes mellitus.

OBJECTIVE: To determine the effects of combined zinc (Zn) and chromium (Cr) supplementation on oxidative stress and glucose homeostasis of people with type 2 diabetes. DESIGN: Tunisian adult subjects with HbA1C > 7.5% were supplemented for 6 months with 30 mg/d of Zn as Zn gluconate or 400 microg/d of Cr as Cr pidolate or combined Zn/Cr supplementation or placebo. The effects of supplementation on plasma zinc (Zn), copper (Cu), selenium (Se), urinary Zn, Cr, plasma thiobarbituric acid reactive substances (TBARS), Cu-Zn superoxide dismutase (SOD) and Se glutathione peroxidase (GPx) in red blood cells, blood lipids and lipoproteins, HbA1C and fasting glucose were measured at the beginning of the study and after six months. RESULTS: At the beginning of the study, more than 30% of the subjects may have been Zn deficient with plasma Zn values less than 10.7 mircomol/L, whereas levels of plasma Cu, Se and antioxidant RBC enzyme activities were in the normal ranges. Following supplementation, there were significant decreases of plasma TBARS in the Cr (13.6%), Zn (13.6%) and Zn/Cr (18.2%) groups with no significant changes in the placebo group. The value for the TBARS of the control healthy Tunisian subjects was 2.08 +/- 0.04 micromol/L and that of the Tunisian subjects with diabetes was 3.32 +/- 0.05 micromol/L. This difference of 1.24 micromol/L between the control group and the subjects with diabetes was reduced from 36% to 50% in the three supplemented groups. Supplementation did not modify significantly HbAIC nor glucose homeostasis. No adverse effects of Zn supplementation were observed on Cu status. HDL cholesterol nor interactions in Zn or Cr. CONCLUSIONS: These data suggest the potential beneficial antioxidant effects of the individual and combined supplementation of Zn and Cr in people with type 2 DM. These results are particularly important in light of the deleterious consequences of oxidative stress in people with diabetes.